Cell Signaling Technology

Product Pathways - PI3K / Akt Signaling

Hamartin/TSC1 Antibody #4906

Applications Reactivity Sensitivity MW (kDa) Source
W IP H M R Endogenous 150 to 170 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Hamartin/TSC1 Antibody detects endogenous levels of total hamartin/TSC1 protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to the sequence of human hamartin. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from NIH/3T3, MDA-MB-468 and PC12 cells, untreated or lambda phosphatase-treated, using Hamartin/TSC1 Antibody.

Background

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that causes symptoms including hamartomas in brain, kidney, heart, lung and skin (1). The tumor suppressor genes TSC1 and TSC2 encode hamartin and tuberin, respectively (2,3). Hamartin and tuberin form a functional complex and are involved in numerous cellular activities such as vesicular trafficking, regulation of the G1 phase of the cell cycle, steroid hormone regulation, Rho activation and anchoring neuronal intermediate filaments to the actin cytoskeleton (4-9). The combination of genetic, biochemical and cell-biological studies demonstrate that the tuberin/hamartin complex functions as a GTPase-activating protein for the Ras-related small G protein Rheb and thus inhibits targets of rapamycin including mTOR. Cells lacking hamartin or tuberin fail to inhibit phosphorylation of S6 kinase resulting in the activation of S6 ribosomal protein's translation of 5'TOP mRNA transcripts (10). Hamartin is phosphorylated by CDK1 (cdc2) at Thr417, Ser584 and Thr1047 in cells in G2/M phase of the cell cycle (11).

  1. Sparagana, S.P. and Roach, E.S. (2000) Curr. Opin. Neurol. 13, 115-119.
  2. van Slegtenhorst, M. et al. (1997) Science 277, 805-808.
  3. No authors listed. (1993) Cell 75, 1305-1315.
  4. Plank, T.L. et al. (1998) Cancer Res. 58, 4766-4770.
  5. Xiao, G. et al. (1997) J. Biol. Chem. 272, 6097-6100.
  6. Tapon, N. et al. (2001) Cell 105, 345-355.
  7. Henry, K.W. et al. (1998) J. Biol. Chem. 273, 20535-20539.
  8. Lamb, R.F. et al. (2000) Nat. Cell Biol. 2, 281-287.
  9. Haddad, L.A. et al. (2002) J. Biol. Chem. 277, 44180-44186.
  10. Manning, B.D. and Cantley, L.C. (2003) Trends Biochem Sci. 28, 573-576.
  11. Astrinidis, A. et al. (2003) J. Biol. Chem. 278, 51372-51379.

Application References

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This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.

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